Study of genetic diseases with neoplastic manifestations and detailed investigation of families at high risk of cancer may help detect environmental and genetic influences in carcinogenesis. Methods include review of prior medical and environmental history; documentation of history; collection and distribution of biological specimens; review of hospital records of patients with selected genetic diseases or neoplasms; and survery of childhood cancer death certificates in the U.S. since 1960. A comprehensive battery of laboratory studies often reveals abnormalities in the cancer patient and apparently normal relatives. For example, in families with apparent excess of lymphoproliferative malignancies, subclinical immune defects were detected; in a family with osteosarcoma, minor bony birth defects and bone marrow dysfunction were discovered. The same approach will be continued, using new laboratory methods and epidemiologic clues from other sources as available.